Hexahydro-1,4,9,9-tetramethyl-4,7-methano-azulenones

ABSTRACT

Novel hexahydro-1,4,9,9-tetramethyl-4,7-methanoazulenones useful as olfactory agents; perfume compositions containing such azulenones; and methods for preparing such azulenones and such compositions.

I United States Patent 11 1 ,679,750

Mookherjee July 25, 1972 HEXAHYDRO-l,4,9,9-TETRAMETHYL- [56] ReferencesCited 4,7-METHANO-AZULENONES UNITED STATES PATENTS [721 Mwkheflu,Matawan, 3,407,225 10/1968 Dunkle .l ..260/586 A x [73] Assignee:International Flavors 8t Fragrances lnc., OTHER PUBLICATIONS New York,NY.

Treibs, Chem Abstracts," Vol. 44, pp. 3945i- 3947a, 1950 1 F11ed= June10, 1968 Brown at al. Chem Abstracts," Vol. 66., p. 648471), (1967).

[21] Appl' 735545 Primary Examiner-Leon Zitver Assistant ExaminerNormanMorgenstern 52 U.S. c1. .260/586 A, 252/89, 252/108, y Haidt & Haffner252/522, 252/DlG. 5, 252/DIG. l3, 252/DIG. 14, 260/617 F, 260/617 M,260/6755, 424/59, 424/65, [57] ABSTRACT /70, 424/76 Novelhexahydro-l,4,9,9-tetramethyl-4,7-methanoazulenones [51] Int. Cl ..C07c49/54 useful as olfactory agents; perfume compositions containing [58]Field of Search ....260/586,' 586 A, 586 R such azulenones; and methodsfor preparing such azulenones and such compositions.

3 Claims, No Drawings HEXAHYDRO-l ,4,9,9-TETRAMETHYL4,7-METHANO-AZULENONES BACKGROUND OF THE INVENTION fragrances to compositions. Forexample, Buchi et al., 84

J.A.C.S. 3205 (I962), show the production of hexahydro-4,9,9-trimethyl-A --4,7-methanoazulenel 2H )-one. The odor of thisketone was not stated. It is found to have a weak woody odor.

THE INVENTION R1 1 ll wherein one of R and R is oxygen and the otherrepresents two hydrogen atoms, R is methyl, or when R is oxygen, methylor methylene, and one of the dashed lines represents a double bond. Italso relates to the use of these unsaturated ketones as olfactory agentsand in perfume compositions, as well as in the preparation of suchcompositions. The novel azulenones of the present invention provideasuperior intense, camphoraceous woody amber fragrance note. Accordingly,smaller quantities can be used to impart a camphoraceous, woody amberfragrance to perfume compositions and to perfumed articles, such assoap, face powder and other articles as disclosed hereinafter.

The novel materials according to the present invention can be consideredas hexahydro derivatives of methanoazulene and are hexahydrol,4,9,9-tetramethyl-A -4,7- methanoazulen-3(2H)-one O l l hexahydro-l,4,9,9-tetramethyl-A" -4,7-methanoazulen-3( hexahydrol-methylene-4,9,9-trimethyl-A -4,7- mcthanoazulen-3 2H )-one hexahydro-l,4,9,9-tetramethyl-A --4,7-methanoazulen-8( (Ill) and mixtures thereof.It will be appreciated that the foregoing structures include the variousstereoisomeric forms.

The unsaturated ketones can be used individually or in admixture.Generally, the ketones are utilized in admixture, and

in many aspects of the present invention a mixture of the four cyclicketones is preferred.

The unsaturated ketones of this invention are useful as olfactory agentsand fragrances. They have a camphoraceous woody amber fragrance in theirown right and can impart this fragrance note to perfume compositions andperfumed articles according to the present invention. They can either beformulated into, or used as components of, perfume compositions.

The term perfume composition is used herein to mean a mixture of organiccompounds, including, for example, alcohols, aldehydes, ketones, estersand frequently hydrocarbons which are proportioned so that the combinedodors of the individual components produce a pleasant or desiredfragrance. Such perfume compositions usually contain: (a) the main noteor the bouquet" or foundation-stone of the composition; (b) modifierswhich round-off and accompany the main note; (0) fixatives which includeodorous substances which lend a particular note to the perfumethroughout all stages of evaporation, and substances which retardevaporation; and (d) top-notes which are usually low-boilingfreshsmelling materials.

In perfume compositions the individual component will contribute itsparticular olfactory characteristics, but the overall effect of theperfume composition will be the sum of the effects of all ingredients.Thus, the individual compounds of this invention, or mixtures thereofcan be used to alter the aroma characteristics of a perfume composition,for example, by highlighting or moderating the olfactory reactioncontributed by other ingredients in the composition.

The amount of mixtures or compounds of this invention which will beeffective in perfume compositions depends on many factors, including theother ingredients, their amounts and the effects which are desired. Ithas been found that perfume compositions containing as little as 2percent by weight of mixtures or compounds of this invention, or evenless, may be used to impart a fine woody amber odor to soaps, cosmeticsand other products. The amount employed can range up to 5-7 percent orhigher and will depend on considerations of cost, nature of the endproduct, the effect desired on the finished product and the particularfragrance sought.

The azulene ketones described herein can be used alone or in a perfumecomposition as olfactory components in detergents and soaps; spacedeodorants; perfumes; colognes; bath preparations such as bath oil, bathsalts; hair preparations such as lacquers, brilliantines, pomades, andshampoos; cosmetic preparations such as creams, deodorants, handlotions, sun screens; powders such as talcs, dusting powders, facepowder; and the like. When used as an olfactory component of a perfumedarticle, as little as 0.01 percent of the novel ketones will suffice toimpart an amber, camphoraceous woody odor. Generally it is'preferred notto use more than 0.5 percent because no additional benefit is obtainedand the fragrance may become unbalanced.

In addition, the perfume composition can contain a vehicle or carrierfor the other ingredients. The vehicle can be an absorbent or adsorbentsolid such as a gum or components for encapsulating the composition.

The novel unsaturated ketones of this invention are prepared byoxidizing l,4,9,9-tetramethyl-A --octahydrowherein the dashed lines, R Rand R, are as set forth above. As further disclosed hereinafter, theoxidation is to provide the keto form as indicated without change in thehydrocarbon skeleton.

beta-Patchoulene is readily prepared according to the method of Batesand Slagel, 84 J.A.C.S. 1307 (1962). The beta-patchoulene utilizedherein as starting material is obtained by treating bulnesol treatingthe patchoulene with an agent which will oxidize a methylene group inthe position alpha to a carbon-carbon double bond. Suitable agents aremetal oxides such as chromium trioxide, selenium dioxide, and the likeand alkali-metal dichromates such as sodium dichromate, potassiumdichromate, and the like. It will be understood by those skilled in theart that materials furnishing these oxidizing agents under the reactionconditions can be used in the practice of this process.

It is frequently desirable to carry out the reaction in an acidicmilieu, and acids suitable for this purpose include both strong mineralacids such as sulfuric acid and the like and organic acids such'asacetic acid, acetic anhydride, and other lower alkanoic acids and theiranhydrides. Thus, the combination of sulfuric acid with alkali-metaldichromates and of acetic acid and/or acetic anhydride with chromiumtrioxide is used. Chromiumtrioxide-acetic acid is the preferredoxidizing agent because of its specificity in oxidizing a methylene to acarbonyl.

The time and temperature at which the reaction is carried out areinterrelated. It has been found that temperatures of from about C toabout 80 C can be used in carrying out the process of the presentinvention. The reaction time is chosen to obtain the desired yields ofthe unsaturated ketones. Thus, it has been found that the reaction canbe carried out for to days at 2030 C or for 20 to 22 hours at 50-60 Cwith good results.

The reaction is preferably carried out in an inert vehicle which willnot be attacked by the reactants under the reaction conditions and whichwill serve to promote contact between the reactants and to moderate'thereaction. The vehicle can be a solvent for reactants. It is preferred tohave t-butanol present.

The amount of oxidizing agent can be varied over a range depending uponthe desired reaction rate, the particular oxidizing agent, the reactionvehicle employed, and the time and temperature of the reaction. It isgenerally preferred that an equimolar or greater quantity of oxidizingagent, based on the amount of patchoulene, be present. The quantity ofacid present should be from 10 to 20 equivalents, based on thebeta-patchoulene.

The reaction can be carried out over a wide range of pressure from subtosuperatmospheric. It is generally preferred to carry out the reactionunder atmospheric pressure.

Depending upon the particular isomer or isomer mixture of ketonesprepared according to this invention, the ketones can be purified and/orisolated as desired. Any unreacted chromic oxidizing agent can bedecomposed with a suitable agent, such as oxalic acid. The finalunsaturated ketone is desirably purified to remove unreacted materials,by-products, color bodies, foreign odor bodies, and the like. Thepurification and/or isolation of the products can be carried out byconventional techniques. Thus, the products can be purified, separated,and/or isolated by distillation, extraction, preparative chromatographictechniques, and the like. It is frequently desirable to wash and dry themixture of ketones prior to final purification and/or isolation.

As disclosed above, the novel unsaturated methanoazulene ketones of thisinvention can be utilized as olfactory agents and in perfume andperfumed articles. They can also be further treated to obtain otheruseful materials. Thus, copending application Ser. No. 735,544 filedJune 10, 1968, in the name of James D. Grossman et al., entitled NovelProcess and Product," discloses methods for the production of per hydroalcohols from the novel unsaturated ketones of this invention. Suchalcohols can be further treated to provide saturated ketones havinggreat utility as olfactory agents.

All parts, proportions, percentages, and'ratios herein are by weight,unless otherwise stated.

The following Examples are given to illustrate embodiments of theinvention as it is presently preferred to practice it. It will beunderstood that these Examples are illustrative and the invention is notto be considered as restricted thereto except as indicated in theappended claims.

EXAMPLE I DIRECT OXIDATION OF BETA-PATCHOULENE TO FORM UNSATURATEDKETONES A: Oxidizing Agent Into a 3-liter reaction flask equipped with areflux condenser, Y-tube, stirrer and nitrogen purge means, 1.2 litersof t-butyl alcohol is introduced. During nitrogen purging, 400 g. ofanhydrous chromium trioxide is added to the t-butyl alcohol over al-hour period. The reaction mass is then dissolved in carbontetrachloride (2 liters) and washed with three 500 cc. portions of waterand dried over anhydrous sodium sulfate. B: Direct Oxidation ReactionInto a l2-liter reaction flask equipped with a reflux condenser,stirrer, Y-tube, thermometer and addition funnel, are placed:

200 g. beta-Patchoulene 2 liters Carbon tetrachloride cc. Aceticanhydride 600 cc. Acetic acid.

The mass is stirred and heated to 50 C.

A solution is obtained by admixing 3% liters of the chromiumoxide/t-butyl alcohol complex prepared as in A above, 160 cc. of aceticanhydride, and 600 cc. of acetic acid. This solution is added dropwiseto the beta-patchoulene solution over a 2 k hour period, whilemaintaining the reaction mass at 50 C. The reaction mass is then stirredfor hours at 50 C.

The reaction mixture is then washed with a solution of 1,500 g. ofoxalic acid in 12 liters of water, twice with 500 cc. of water,neutralized with saturated Na CO solution and then again twice withwater. The washed material is dried over anhydrous sodium sulfate andconcentrated under vacuum.

The crude concentrated material (195 g.) is distilled at ll3l48 C and1.8-0.8 mm Hg to yield a mixture ofl. 11, 111, and IV. This mixture hasa pleasant woody-amber camphoraceous patchouli-like odor. The individualcompounds are separated by gas-liquid chromatography (GLC) (20 feet X 74 feet column containing 5 percent Carbowax 20M" polyethylene glycolcoated on Anakrom ABS" silanized acid-washed calcined diatomaceous earthmade by Analab, Inc., Hamden, Conn.; flow rate, 100 microliters/minute;column temperature, 220 C; chart speed, 15 in./hour).

I has a strong patchouli camphor aroma.

I] has an excellent minty-camphory -woody odor, and a patchouli note aswell as a peppery fragrance note. ll is obtained by means offractionaldistillation.

lll has an ambery-cedar woody aroma and a desirable incense quality.

IV has a woody-camphory odor.

According to GLC analysis, the ratio of lzlllzlV is approximately 17.7percent: 65.0 percent: l7.2 percent.

lnfrared analysis of the four materials yields the following data:

Table 1 shows the absorption bands (in cm") of various structuralfeatures of the four compounds.

Mass spectra of the four materials show peaks (in order of decreasingintensity) on a Consolidated Electrodynamics Corp. Model 21-103Cinstrument:

Material Parent Peaks Other Peaks I 218 l75,41,133,69

11 218 41,39.190,109,9l,45 III 218 l2l,l22,4l,39,9l.

1V 2.16 173,4l,2l6,31,45,69

Nuclear magnetic resonance (NMR) analysis confirms the structures ofcompounds I-IV as given above. NMR analyses for specific stereo isomersof each of compounds I-IV are as follows, wherein the number and H inparentheses indicates the number of hydrogen atoms attributable to theband:

lsonur (n) of Formuln l 11' em Singlet time. an). .n

Il :u-.ing ()j olupounil ll U I 'lwo singlets nl. 50

1\ n|ul5Hll7,(till). ll (I! llu & Singlet nt (18 H7, (3H). I F (llh- (llIl-uciug (1 ()1 llrolul singlet at 106 I llz. (lll; (3'

lsonur (n) 01 Formula 111 'lwo singlets tit 51 I :nulM llz (fill). (illn(Z- Ulla Doublets nt 58 and ti l I llz. Ulla-"(#43 11 ISOl ltl (h) ofFormula 111 Singlet nth 1 ll7. (till). I (lllzrtll (lllzi Singlet nt 65111.5. I

out 0 "(1.41 ll Ella I H Doublct at 63 and 70 (1:

Hz. CII -|-O C- Compound IV 0 Two singlets at 60 CII3CC H l 1\ and 55 Hz(611). I Singlet at 78 Hz (3H). OH3-CC=C l [Facing 0:0]

Broad singlet at Hz (2H). C=C-CI-I Broad doublet at 298 C CH; I17,(211).

The presence of conjugated carbonyl in compounds I and IV is indicatedby X m at 274 and 242 mg, respectively, in the ultraviolet. spectra.

EXAMPLE II The ketone mixture prepared in Example I is dissolved inalcohol to obtain a 10 percent solution, and a second 10 percentsolution is prepared by dissolving hexahydro-4,9,9-trimethyl-A--4,7-methanoazulen-l(2I-I)-one (the trialkyl azulene material producedby Buchi et al., supra, hereinafter called the trialkyl azulene"material) in alcohol. A 10 percent solution of ketones preparedaccording to Example I has a strong camphoraceous woody amber fragrance,whereas the other solution is almost odorless. A I percent solution ofthe ketones prepared in Example I displays a distinct, recognizablepatchouli-like odor and is still considerably stronger than the 10percent solution of the trialkyl azulene material.

Similar results are obtained with the individual ketones I, II, III andIV prepared according to the present invention.

EXAMPLE III PERFUME COMPOSITION A further comparison is carried oututilizing the following perfume base compositions:

Ingredient Benzyl Acetate Petitgrain Absolute Phenyl Ethyl AlcoholBergamot Cananga Oil Java Opoponax Oil Geraniol Citronellol Myrrh OilTincture Castoreum 20% Musk Xylol Sandalwood Oil Vanillin CoumarinAmount (Parts) To separate samples of the foregoing base are added (A) 5parts of the trialkyl azulene material, (B) 5 parts of the ketonemixture of Example I, and (C) 5 parts of patchouli oil.

Sample A shows substantially no change in aroma from the basecomposition, while sample B shows the woody, oriental fragrance effectresembling that obtained by the use of genuine patchouli oil (Sample C).

EXAMPLE IV PERFUME COMPOSITION A perfume composition is prepared withthe following ingredients:

Ingredient Parts Vetivert Oil 40 Ketone Mixture of Example I 60Sandalwood Oil I00 Rose Geranium Oil 200 Musk Extract (3%) 25 CivetExtract (3%) 25 Benzyl-iso-Eugenol I00 Coumarin I00 Heliotropin 50 Boisde Rose Oil 200 Benzoin Resin I00 I000 The perfume composition exhibitsan excellent woody fragrance. When the ketone mixture is omitted, thecomposition lacks the woody, amber fullness of the complete perfumecomposition of this Example.

It will be understood from the present description that the individualketones of the present invention can be used separately or incombination with each other to provide a good intense camphoraceouswoody fragrance note.

In the following Examples, the soap base and soap chips used areunperfumed sodium-based toilet soaps made from tallow and coconut oil.The detergent powder is a material obtained from Lever Bros. Co. andsold under the trademark Rinso." The liquid detergent is a productmanufactured by Ultra Chemical Co., and is known as P-87 liquiddetergent.

EXAMPLE v PREPARATION OF SOAP COMPOSITION One hundred grams of soapchips are mixed with 1 gram of the perfume composition of Example IVuntil a substantially homogeneous composition is obtained. The perfumedsoap composition manifests an excellent woody, amber, patchouli odorcharacter.

EXAMPLE VI PREPARATION OF A DETERGENT COMPOSITION A total of grams ofdetergent powder is mixed with 0.15 grams of the perfume composition ofExample IV until a substantially homogeneous composition is obtained.This composition has an excellent woody, amber odor.

EXAMPLE VII PREPARATION OF A COSMETIC POWDER COMPOSITION A cosmeticpowder is prepared by mixing in a ball mill 100 grams of talcum powderwith 0.25 grams of the mixture obtained from the process of Example I.The powder has an excellent camphoraceous, woody, patchouli-like odor.

EXAMPLE VIII PERFUMED LIQUID DETERGENT wherein R is methyl or methylene,and one of the dashed lines represents a double bond. I I

2. An unsaturated ketone according to claim 1, wherein R is methyl.

3. An unsaturated ketone according to claim I, wherein R is methylene,and the dashed line which is beta to R is a double bond.

CERTIFICATE OF CORRECTION Patent NO. 3,679,750 Dated July 25, 1972lnvento D.

It is certified that error appears in the above-identified patent andthat said Letters Patent are hereby corrected as shown below:

Col. 1, lines 35-55 correct Table 1 to read as .follows:

TABLE I Compound I I I 111 I 7 5-Membered 1625,1695 1740 5 None 1700ring carbonyl (conjugated) (non-conjugated) (conjugated) Methylene 14251425 None 1432 Alpha to carbonyl gem-Dimethyl 1370-90 1370-90 1370-901390, and l or 2 (2 Me (2 Me (2 Me (1 Me Group) methyl group Groups)Groups) Groups) 6-Membered None None 1625 None conjugated 1670 ringketone Conjugated None None None 1570,1630 C=C bonds exo-Vinylidene NoneNone None 885,3080

in 5-m'embered ring (Continued) USC OMM-DC 60376-969 h u s covcnrmzmPRINYING OFFICE I969 0-166-131 UNITED STATES PATENT OJQIC 1 F. e A. IFF2028B CbRTlr IQATQL 0F LDRRECTEON Patent No. 3, 679 750 1 Dated July 251972 Inventor(s) BRAJA M OKHERJEE It is certified that error appears inthe above-identified patent and that said Letters Patent are herebycorrected as shown below:

Page 2 Col. 6, Lines 5-10, correct Formula I to read:

Col. 6, line 40, correct Formula III to read:

Claim 1, col. 8, line 55, correct the formula to read:

Signed and sealed this 6th day of February 1973.

(SEAL) Attest:

ROBERT GOITSCHALK Commissioner of Patents EDWARD MQFLETCHER R. AttestingOfficer

2. An unsaturated ketone according to claim 1, wherein R3 is methyl. 3.An unsaturated ketone according to claim 1, wherein R3 is methylene, andthe dashed line which is beta to R3 is a double bond.